PROJECT ABSTRACT The record flooding that occurred in Houston after Hurricane Harvey caused uncontrolled releases into the environment from over a dozen Superfund sites and several chemical/petroleum facilities. Under our Parent Time-sensitive R21, we worked with affected communities to administer health questionnaires, deployed wristbands to detect chemical exposures, and collected biosamples for microbiome analysis at 1- and 12-months after flooding. In these initial studies we identified a novel microbiome:environment interaction linked to allergic health outcomes. Under this Administrative Supplement, we will build on this work with longitudinal time- sensitive sampling of nasal, oral and gut biospecimens three years post-Hurricane Harvey. These biospecimens and microbiome data will be used for continuing disaster research response (DR2) activities, and stored as a unique resource for future microbiome:environment interaction studies. They will also be integrated with chemical exposure data obtained from wristband monitoring devices, and health outcome data from questionnaires administered to study participants at corresponding timepoints. Our Overarching Hypothesis is that microbiome:environment interactions play a role in the long-term health effects following a flood-related disaster. If correct, this would further support that the microbiome can serve as a target for such environmental exposures, or an indicator for actionable, post-disaster activities. In Specific Aim 1, we will collect environmental and biological samples from participants at the 3-year timepoint post-flooding, expanding our biospecimen collection to include samples reflective of a longer-term health outcomes. In Specific Aim 2, we will profile these samples via metagenomic sequencing and test whether microbiome-exposure or microbiome-health outcome relationships identified at earlier timepoints persist long-term. These include continued associations of the nasal mycobiome with fungi found in the home and the relationship between the gut microbial community, mold exposure, and allergic symptoms. Finally, in Specific Aim 3 we will integrate 1-month, 12-month and 3-year microbiome data with short- intermediate- and long-term health assessments and chemical exposure studies being conducted by our collaborators to identify novel microbiome:environment interactions. We will ask whether microbiome analyses from biospecimens collected over short-, medium-, and long-term correlate with chemical exposures captured by wristbands or other environmental monitoring and jointly inform health outcomes. In the future, these studies are expected to provide Preliminary Data for research aimed at 1) better understanding the role of the microbiome on post-disaster health outcomes, 2) identifying microbiome-based biomarkers of exposure(s) and/or health effects, and 3) improving decision- making by stakeholders and DR2 activities in response to future flood-related disasters.